There is strong evidence that measurement of the DNA content and proliferative patterns of rectal mucosal cells in asymptomatic individuals can serve as a valid biomarker of early neoplastic changes occurring within other areas of the colorectum. We have developed a diagnostic approach which combines a non-invasive method for the collection of superficial rectal cells with flow cytometric techniques to measure the DNA proliferative patterns of these cells. In a preliminary series of patients, we were able to correctly predict risk in 5/5 normal subjects and 7/9 high risk individuals. It is our hypothesis that FCM measurement of the DNA ploidy levels and proliferative patterns of superficial rectal mucosal cells obtained by rectal scraping will provide an accurate biomarker of early malignant changes within the large bowel. We propose: I. To examine the RNA and DNA content of superficial rectal mucosal cells in a large series of individuals at high risk for the development of colorectal cancer. II. To correlate the DNA abnormalities observed in the rectal mucosal cells of high risk individuals with the clinical and historical risk factors associated with these individuals. III. To extend these studies to examination of the general population.